Contrast-enhanced MRI with new biodegradable macromolecular Gd(III) complexes in tumor-bearing mice

Yuda Zong, Xinghe Wang, K. Craig Goodrich, Aaron M. Mohs, Dennis L. Parker, Zheng Rong Lu

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The structures of polydisulfide-based biodegradable macromolecular Gd(III) complexes were modified to improve their in vivo retention time and MRI contrast enhancement. Steric hindrance was introduced around the disulfide bonds to control their access to free thiols in order to alter the degradation rate of the copolymers. Two new macromolecular agents, (Gd-DTPA)-cystine copolymers (GDCP) and (Gd-DTPA)-cystine diethyl ester copolymers (GDCEP), were prepared. Both agents were readily degraded in vitro and in vivo by the disulfide-thiol exchange reaction, but at a slow rate. The introduction of COOH and COOEt groups slowed down the degradation of the copolymers in the incubation with 15 μM cysteine. Metabolic degradation products were identified by matrix-assisted laser desorption/ ionization time-of-flight (MALDI-TOF) mass spectrometry in the urine samples from rats injected with the agents. The T1 relaxivity (r1) was 5.43 mM-1s-1 for GDCP, and 5.86 mM-1s-1 for GDCEP, respectively, at 3T. MRI contrast enhancement of both agents was studied in nude mice bearing MDA-BM-231 human breast carcinoma xenografts, on a Siemens Trio 3T scanner. The modified agents resulted in more significant contrast enhancement in the blood pool and tumor periphery than (Gd-DTPA)-cystamine copolymers (GDCC) and a low-molecular-weight control agent, Gd-(DTPA-BMA), at a dose of 0.1 mmol-Gd/kg. The results demonstrate that the structural modification of the biodegradable macromolecular Gd(III) complexes resulted in a relatively slow degradation of the macromolecules and significantly improved in vivo contrast enhancement. The modified agents show promise for use in investigations of blood pool and cancer by contrast-enhanced (CE) MRI.

Original languageEnglish (US)
Pages (from-to)835-842
Number of pages8
JournalMagnetic Resonance in Medicine
Volume53
Issue number4
DOIs
StatePublished - Apr 2005

Keywords

  • Biodegradation
  • Contrast agents
  • Macromolecular Gd(III) complexes
  • Polydisulfide
  • Tumor MRI

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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